ABSTRACT: Stem cells respond to both physical and biochemical changes in their stem cell niche. An ideal scaffold for tissue engineering application should mimic the microenvironment for natural tissue development and present the appropriate biochemical and topographical cues in a spatially controlled manner. Studies have shown that physical forces from the substrate topography play a role in stem cell proliferation, migration and cell fate determination. Our research group is interested in studying the interactions of adult and pluripotent stem cells with nanotopography, the mechanism of the topography-induced cell behavior and how to apply this knowledge to direct stem cell differentiation for tissue engineering applications. In this presentation, nanotopography-regulation on adult and embryonic stem cells (ESCs) will be presented as examples of applying nanotopography in stem cell regulation.
A Multi ARChitectural (MARC) chip containing fields of various geometries and size was developed to investigate the influence of topography geometry on differentiation. Human ESCs and murine neural progenitor cells grown on anisotropic patterns derived a significantly higher percentage of Tuj1 and MAP2 positive cells, while isotropic patterns enhanced glial differentiation.
In attempt to understand the sensing mechanisms for nanotopography, we investigated the differentiation of human mesenchymal stem cell (hMSC) and demonstrated the nanotopography-induced differentiation through cell mechanotransduction is modulated by the integrin-activated focal adhesion kinase (FAK). In addition, our mechanistic study confirmed that this regulation was dependent upon actomyosin contractility, suggesting a direct force-dependent mechanism. The temporal presentation of topography also plays a significant role in the differentiation. In a study of the effect of temporal presentation of topography during hESC neuronal differentiation, our results suggested that the topography contact during the differentiation period is necessary and significant for topography-induced differentiation.
Examples of nanotopography-modulation on cell behaviors for tissue-engineering applications will be discussed in the last part of the presentation.
Bio-sketch: Evelyn Yim received her Bachelor of Applied Science in Engineering Science and Master of Applied Science in Chemical Engineering and Applied Chemistry at the University of Toronto, before she pursued her Ph.D. in the Biomedical Engineering at the Johns Hopkins University. Subsequently, she performed her post-doctoral training at the Johns Hopkins School of Medicine and in the Department of Biomedical Engineering at Duke University before she joined the National University of Singapore as a faculty in the Department of Biomedical Engineering and Department of Surgery in 2007. Her research interests in understanding how the chemical and biomechanical cues influence stem cells behavior spurred her to join the Mechanobiology Institute Singapore in 2009. Experienced with nanofabrication technologies and stem cell culture techniques, Evelyn and her group are interested to apply the knowledge material-stem cell interaction to direct stem cell differentiation and tissue regeneration for neural, vascular and corneal tissue engineering.